Prevention of hypoxic liver cell necrosis by in vivo human bcl-2 gene transfection.
Prevention of hypoxic cell death is a key to successful liver transplantation. We developed a new method for preventing liver hypoxic cell death by introducing an anti-cell death gene directly into rat livers. When the human bcl-2 gene (hbcl-2) was directly transfected into rat livers together with non-histone chromosomal protein high mobility group 1 (HMG1) by the hemagglutinating virus of Japan (Sendai virus; HVJ)-liposome method, human Bcl-2 protein (hBcl-2) was efficiently expressed. Electron microscopy and fluorescence microscopy revealed that hepatocytes expressing exogenous hBcl-2 were almost completely protected the hypoxic cell necrosis. The expression of the hBcl-2 also inhibited activation of caspase-3 (-like) proteases and liver dysfunction. Thus, we conclude that transfection of the hbcl-2 gene through HVJ-liposome method is useful to prevent liver cell necrosis induced by hypoxia. This finding could lead to new strategies to avoid the hypoxic cell death, the major problem in liver transplantation.
Yamabe
K
K
First Department of Surgery, Osaka University Medical School, Suita, Japan.
Shimizu
S
S
Kamiike
W
W
Waguri
S
S
Eguchi
Y
Y
Hasegawa
J
J
Okuno
S
S
Yoshioka
Y
Y
Ito
T
T
Sawa
Y
Y
Uchiyama
Y
Y
Tsujimoto
Y
Y
Matsuda
H
H
D000818:Animals; D053148:Caspase 3; D020169:Caspases; D016923:Cell Death; D015687:Cell Hypoxia; D003546:Cysteine Endopeptidases / Q000378:metabolism; D004789:Enzyme Activation; D019254:Genes, bcl-2; D006801:Humans; D007763:Lac Operon; D008099:Liver / Q000293:injuries / Q000378:metabolism* / Q000473:pathology*; D016031:Liver Transplantation; D008297:Male; D008854:Microscopy, Electron; D009336:Necrosis; D009926:Organ Preservation; D010477:Perfusion; D051381:Rats; D017208:Rats, Wistar; D014162:Transfection
C505407:CASP3 protein, human; C505410:Casp3 protein, rat; D053148:Caspase 3; D020169:Caspases; D003546:Cysteine Endopeptidases